小柯机器人

多重内源基因激活增强抗肿瘤免疫
2019-10-15 14:57

美国耶鲁大学医学院Sidi Chen课题组研究发现,CRISPRa对内源性基因的多重激活可产生有效的抗肿瘤免疫。 2019年10月14日,《自然—免疫学》在线发表了这项成果。

研究人员创建了多重激活内源性基因的免疫疗法(MAEGI),这是一种新形式的免疫疗法,可通过肿瘤中内源性基因的多重激活来引发抗肿瘤免疫力。

研究者利用CRISPR的激活(CRISPRa)直接增强内源基因的原位表达,增强了肿瘤抗原的表达,从而导致了显著的抗肿瘤免疫反应。将其作为基于细胞的疫苗接种策略,在预防和治疗肿瘤方面均显示出功效。利用腺病毒表达 CRISPRa文库可引发针对多种癌症类型的强大抗肿瘤免疫。针对突变基因的靶向集可在局部和远处根除大部分已建立的肿瘤。这种治疗方式导致肿瘤微环境的改变,其特征在于增强的T细胞浸润和抗肿瘤免疫反应。

多重内源基因激活是一种通用且高度可扩展的策略,可引发针对癌症的有效免疫反应,这不同于现有的癌症疗法。

据介绍,免疫疗法改变了癌症的治疗方法。然而,当前的免疫治疗方式面临各种限制。

附:英文原文

Title: Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity

Author: Guangchuan Wang, Ryan D. Chow, Zhigang Bai, Lvyun Zhu, Youssef Errami, Xiaoyun Dai, Matthew B. Dong, Lupeng Ye, Xiaoya Zhang, Paul A. Renauer, Jonathan J. Park, Li Shen, Hanghui Ye, Charles S. Fuchs, Sidi Chen

Issue&Volume: 2019-10-14

Abstract: 

Immunotherapy has transformed cancer treatment. However, current immunotherapy modalities face various limitations. In the present study, we developed multiplexed activation of endogenous genes as an immunotherapy (MAEGI), a new form of immunotherapy that elicits antitumor immunity through multiplexed activation of endogenous genes in tumors. We leveraged CRISPR activation (CRISPRa) to directly augment the in situ expression of endogenous genes, and thereby the presentation of tumor antigens, leading to dramatic antitumor immune responses. Deploying this as a cell-based vaccination strategy showed efficacy in both prophylactic and therapeutic settings. Intratumoral adeno-associated virus delivery of CRISPRa libraries elicited strong antitumor immunity across multiple cancer types. Precision targeting of mutated gene sets eradicated a large fraction of established tumors at both local and distant sites. This treatment modality led to alterations in the tumor microenvironment, marked by enhanced T cell infiltration and antitumor immune signatures. Multiplexed endogenous gene activation is a versatile and highly scalable strategy to elicit potent immune responses against cancer, distinct from all existing cancer therapies.

DOI: 10.1038/s41590-019-0500-4

Source: https://www.nature.com/articles/s41590-019-0500-4

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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